Some of the most common pathogens associated with invasive fungal infections are the opportunistic yeasts, such as Candida spp. and Aspergillus spp. Thousands of Candida spp. cells can be present in an individual, primarily in the gastrointestinal tract, as a harmless commensal organism. However, Candida spp., such as C. albicans, cause opportunistic fungal infections. Infections can be localized, such as a vaginal infection or an oral infection, both of which cause a considerable degree of discomfort. In patients whose immune system is severely compromised (for example, prematurely born infants, patients infected with HIV, patients with hematological disease or cancer, and burn patients), the yeast can turn into a deadly pathogen causing systemic infections. Aspergillus spp., such as A. niger, are also opportunistic fungi which under certain conditions lead to infection, e.g., aspergillosis.
Currently available drugs for the treatment of fungal infections include amphotericin B, a macrolide polyene that interacts with fungal membrane sterols, flucytosine (5FC), a fluoropyrimidine that interferes with fungal protein and DNA biosynthesis, and a variety of azoles (e.g., triazoles and imidazoles such as ketoconazole, itraconazole, and fluconazole) that inhibit fungal membrane-sterol biosynthesis. Even though amphotericin B has a broad range of activity and is viewed as the “gold standard” of anti-fungal therapy, its use is limited due to infusion-related reactions and nephrotoxicity. Flucytosine usage is also limited due to the development of resistant microbes and its narrow spectrum of activity. The widespread use of azoles is causing the emergence of clinically-resistant strains of Candida spp.
The development of new anti-fungal treatment regimens has been a continuing challenge. What is needed in the art are additional anti-microbial, e.g., anti-fungal agents.